This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The epidermal growth factor receptor (EGFR) is a major target for drugs in treating lung carcinoma. Structural studies have demonstrated dramatic conformational transitions that are critical to its drug binding and activation. It is known that EGFR mutations promote its conformational changes and hence affect drug efficacy;indeed, various drugs have been developed that target different EGFR conformations. Using Anton and Desmond here we plan to study these conformations and their dynamics as well as the effects of controlled mutations in order to understand the activation mechanisms in the EGFR kinase domain.